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Synfacts 2023; 19(02): 0187
DOI: 10.1055/s-0042-1751830
Innovative Drug Discovery and Development

“Click-to-Release” Biorthogonal Chemophototherapy

Contributor(s):
Dirk Trauner
,
Tufan K. Mukhopadhyay
Sun J, Zhang X, Wang X, Peng J, Song G, Di Y, Feng F, *, Wang S. * Nanjing University and Institute of Chemistry, Chinese Academy of Sciences, Beijing, P. R. of China
Dithiol-Activated Bioorthogonal Chemistry for Endoplasmic Reticulum-Targeted Synergistic Chemophototherapy.

Angew. Chem. Int. Ed. 2022;
61: e202213765
DOI: 10.1002/anie.202213765.
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Key words

Sonogashira cross-coupling - benzothiadiazole - organic nitrite donors

Significance

Intracellular nitrite release from organic nitrite donors is an emerging approach for inducing apoptosis via reactive nitrogen species (RNS) formation. RNS are known to form cytotoxic peroxynitrite (OONO–) by reacting with intracellular ROS. Here, the authors present a synergistic biorthogonal approach using 5-nitro benzothiadiazole (BTD) as the nitrite donor tethered to the endoplasmic reticulum (ER)-targeting drug nonivamide.


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Comment

This biorthogonal ‘click-to-release’ approach involves an SNAr reaction by a thiol group of the dithiol Gal-SS to release nonivamide, which causes ER stress. Another subsequent SNAr releases the nitrite through a stabilized Meisenheimer complex, which unmasks the fluorescence of BTD. Upon irradiation, BTD sensitizes singlet oxygen to generate ROS and synergistically causes apoptosis in liver cancer cells (HepG2).


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Publication History

Article published online:
17 January 2023

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